ERX-245

ERX-245 is a potent, orally active small molecule estrogen receptor (ER) coregulator binding inhibitor designed to target both wild-type and mutant estrogen receptor alpha (ERalpha/ESR1), including the therapy-resistant Y537S and D538G mutations. Developed by researchers at the University of Texas System (including UT Southwestern Medical Center, UT Health San Antonio, and UT Dallas), ERX-245 is a structurally optimized analogue of ERX-11 with improved polarity, solubility, and pharmacokinetic properties. Unlike classic selective estrogen receptor degraders (SERDs) like fulvestrant, which rapidly degrade ERalpha, ERX-245 decreases mutant ERalpha protein levels over a 24-hour period. It has demonstrated significant preclinical efficacy in reducing tumor growth, invasion, and metastasis in subcutaneous xenograft, patient-derived xenograft (PDX), and metastatic models of therapy-resistant breast cancer, both as a monotherapy and synergistically in combination with CDK4/6 inhibitors.